Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.65363932
In this work , the interaction of CaM with a 23 amino acid residue synthetic peptide , encompassing the CaM binding domain of constitutive rat cerebellar nitric oxide synthase ( cNOS ) , was investigated by various NMR methods . 0.65363932^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.72201445
Nonetheless , the constitutive NOS isoforms , regulated by calcium fluxes and interaction with calmodulin , may also enhance NO production . 0.72201445^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.53897088
A recent crystallographic study mapped the interaction of CaM with endothelial NOS ( eNOS ) using a 20 residue peptide comprising the binding site within eNOS . 0.53897088^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :1.2509008
Accordingly , we showed that early VEGF stimulation first leads to the Ca ( 2+ ) / calmodulin disruption of the caveolin eNOS complex and promotes the association between eNOS and hsp 90 . eNOS bound hsp 90 can then recruit VEGF activated ( phosphorylated ) Akt to the complex , which in turn can phosphorylate eNOS . 1.2509008^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.87955736
We further create a series of fusion proteins and use FRET imaging methods to study the interactions between eNOS and its obligate allosteric activator protein calmodulin . 0.87955736^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
In this work , we have used `` isotope edited ' ' Fourier transform infrared spectroscopy to study the interaction of CaM with synthetic peptides resembling the CaM binding domains of myosin light chain kinase ( MLCK ) , constitutive nitric oxide synthase ( cNOS ) , and caldesmon ( CaD ) . ^^^ Upon complex formation , the amide 1 bands of the CaM binding domains of MLCK and cNOS shift 4 cm 1 toward higher frequency ( to approximately 1648 cm 1 ) , and have a narrower bandwidth compared to the peptide in aqueous solution . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
L NG Nitroarginine ( NA ) inhibited both the L arginine oxidation and the L arginine independent NADPH oxidation reactions catalyzed by the calcium / calmodulin dependent constitutive nitric oxide synthase ( cNOS ) from bovine brain . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Our data demonstrate that ANG 2 stimulates NO release by activation of Ca2+ / calmodulin dependent cNOS via AT 1 receptors in bovine ECs . . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Nitric oxide synthases ( NOSs ) are classified functionally , based on whether calmodulin binding is Ca2+ dependent ( cNOS ) or Ca2+ independent ( iNOS ) . ^^^ Synthetic peptides derived from the 45 amino acid insert of endothelial NOS were found to potently inhibit binding of calmodulin and activation of cNOS isoforms . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
The activation of cNOS is known to be Ca2+ and calmodulin dependent . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Yeast cNOS was activated in the presence of calmodulin and arginine , whereas it was inhibited by L NAME , a mammalian NOS inhibitor . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Nitric oxide ( NO ) is produced by nitric oxide synthases ( cNOS and iNOS ) in endothelial cells upon stimulation by various agents like Ca ( 2+ ) calmodulin , cytokines and TNF . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
The cNOS , which is constitutively expressed in endothelial cells and central and peripheral neuronal cells , requires both calcium and calmodulin for its activation . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
NO production by the endothelial and neuronal isoforms of nitric oxide synthase ( cNOS ) is regulated on a moment to moment basis by calmodulin binding , triggered by transient elevations in intracellular free calcium levels . ^^^ Herein we summarize our present knowledge and speculate on mechanisms by which calmodulin and the autoinhibitory peptide conspire to regulate cNOS activity . . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
To examine such a hypothesis , we used peptides from the autoregulatory domains of CaM kinase 2 ( CK 291 317 ) and cNOS ( the constitutive nitric oxide synthase ; cNOS 725 747 ) as probes for the calcium dependent activation of murine BKCa channels transiently expressed in HEK 293 cells . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Exercise training enhanced cNOS activity , the protein expression of both neuronal nitric oxide synthase ( nNOS ) and calmodulin , and NADPH cytochrome c reductase activity in the homogenates of islets . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
The interactions of neuronal nitric oxide synthase ( nNOS ) with calmodulin ( CaM ) and mutant forms of CaM , including CaM troponin C chimeras , have been previously reported , but there has been no comparable investigation of CaM interactions with the other constitutively expressed NOS ( cNOS ) , endothelial NOS ( eNOS ) , or the inducible isoform ( iNOS ) . ^^^ CaM activates the cNOS enzymes by a mechanism other than stimulating electron transfer into the oxygenase domain . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
We report here that NADPH analogs such as 2 ' 5 ' ADP , ATP , and 2 ' AMP paradoxically activate constitutive calcium / calmodulin regulated nitric oxide synthases ( cNOS ) , including the endothelial isoform ( eNOS ) and the neuronal isoform ( nNOS ) . ^^^ Effects of these analogs on cNOS ' s include increasing the electron transfer rate to external acceptors , as assessed by cytochrome c reductase activity in the absence of calmodulin . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Four different mutant CaM proteins were used to investigate the role of the two CaM EF hand pairs in the binding and activation of the mammalian inducible NOS ( iNOS ) and the constitutive NOS ( cNOS ) enzymes , endothelial NOS ( eNOS ) and neuronal NOS ( nNOS ) . ^^^ Our results show that the N terminal EF hand pair of CaM contains important binding and activating elements for iNOS , whereas the N terminal EF hand pair in conjunction with the central linker region is required for cNOS enzyme binding and activation . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Constitutive NOS ' s in endothelium and neurons are activated by agonist induced elevation of Ca2+ and resultant binding of calmodulin ( CaM ) . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
The constitutive NOS peptide binds to CaM in a calcium dependent manner with 1 : 1 stoichiometry as determined by polyacrylamide gel electrophoresis of the peptide CaM complex in 4 M urea . ^^^ Binding of the constitutive NOS peptide inhibits the stimulatory effect of CaM on cyclic nucleotide phosphodiesterase . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
As has been shown for all constitutive NOS isozymes , the purified NOS was absolutely dependent on calcium and calmodulin . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
The enzyme , when purified from a bovine retina extract , has an apparent molecular mass of 160 kDa and resembles the neuronal constitutive NOS type 1 with respect to Ca ( 2+ ) calmodulin sensitivity , Km value and inhibition by analogues of L arginine . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Salivary gland NOS produced in a baculovirus system showed NOS activity and demonstrated that salivary gland NOS was soluble and was Ca2+ and calmodulin dependent , similarly to mammalian constitutive NOS isoforms . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Moreover , polyacrylamide gel electrophoresis studies suggest that melatonin can interact with calmodulin modifying the binding of the peptide to the synthetic NOS peptide encompassing the calmodulin binding domain of constitutive NOS from rat cerebellum , the natural mechanism by which calmodulin activates cerebellar NOS . . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Neuronal nitric oxide synthase ( NOS ) and endothelial NOS are constitutive NOS isoforms that are activated by binding calmodulin in response to elevated intracellular calcium . ^^^ To study a possible link between the presence of these additional polypeptide segments in constitutive NOS enzymes and their calcium dependent calmodulin activation , three deletion mutants were created . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
CALM 1 inhibited , at all the concentrations tested ( 0 . 01 1 mM ) , both the inducible and constitutive NOS ( IC ( 50 ) 98 microM and 56 microM , respectively ) , while CALM 2 ( 0 . 01 1 mM ) was ineffective on both isoforms . ^^^ CALM 1 inhibited , at all the concentrations tested ( 0 . 01 1 mM ) , both the inducible and constitutive NOS ( IC ( 50 ) 98 microM and 56 microM , respectively ) , while CALM 2 ( 0 . 01 1 mM ) was ineffective on both isoforms . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
The constitutive NOS isoforms ( cNOSs ) are regulated by calmodulin ( CaM ) , which binds at elevated concentrations of free Ca ( 2+ ) , whereas the inducible isoform binds CaM irreversibly . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Simultaneous administration of 10 micro M ( S ) 2 amino ( 1 iminoethylamino ) 5 thiopentanoic acid ( GW 274150 ) , a specific NOS 2 inhibitor , together with removal of Ca ( 2+ ) and calmodulin ( CaM ) from the assay buffers , known to interfere with the activity of constitutive NOS isoforms , caused a reduction in NOS activity ( 17 . 4 + / 1 . 2 pmol / mg protein / 30 min ) . 10 micro M GW 274150 reduced NOS activity to 41 . 6 + / 4 pmol / mg protein / 30 min , while Ca ( 2+ ) / CaM withdrawal reduced basal NOS activity to 45 . 8 + / 5 pmol / mg protein / 30 min . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
The NO synthases ( EC 1 . 14 . 13 . 39 ) isolated from neurons or endothelium are calmodulin dependent . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Nitric oxide synthase ( EC 1 . 14 . 13 . 39 ) binds arginine and NADPH as substrates , and FAD , FMN , tetrahydrobiopterin , haem and calmodulin as cofactors . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Nitric oxide synthase ( EC 1 . 14 . 13 . 39 ) catalyses the conversion of arginine , NADPH and oxygen to nitric oxide and citrulline , using haem , ( 6R ) 5 , 6 , 7 , 8 tetrahydro l biopterin ( tetrahydrobiopterin ) , calmodulin , FAD and FMN as cofactors . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
To study the structural basis of the difference in Ca2+ sensitivity , we have designed synthetic peptides of minimal lengths derived from the calmodulin binding domain of endothelial NOS ( eNOS ) and that of macrophage NOS ( iNOS ) . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Like the neuronal isoform , endothelial NOS requires binding of Ca2+ / calmodulin to achieve Vmax NO synthase activity ; however , we observed a basal level of NO synthesis even when Ca2+ / calmodulin was omitted and 0 . 5 mM EDTA was present in the assay solution . ^^^ Moreover , endothelial NOS demonstrates a high affinity bonding interaction with calmodulin such that the enzyme as purified has a NO synthase activity at about 80 % of Vmax . ^^^ Thus , the enzymatic synthesis of NO from L arginine by endothelial NOS appears to be partially regulated by binding of both calmodulin and substrate . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
The contraction coupled NO release may be mediated through a mechanism distinct from the Ca ( 2+ ) calmodulin dependent endothelial NOS pathway . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Caveolin , the principal structural protein in caveolae , interacts with endothelial NOS ( eNOS ) leading to enzyme inhibition by a reversible process modulated by Ca++ calmodulin . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Here , the crystallographic structure of Ca ( 2+ ) loaded CaM bound to a 20 residue peptide comprising the endothelial NOS ( eNOS ) CaM binding region establishes their individual conformations and intermolecular interactions , and suggests the basis for isozyme specific differences . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Tissue levels of connexins 40 , 43 ( major components of gap junction ) , inducible NOS ( iNOS ) , endothelial NOS ( eNOS ) and eNOS regulator proteins such as calmodulin , heat shock protein 90 ( hsp 90 ) and caveolin 1 were also examined using Western blot . 2 . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
The inhibitors of phospholipase C ( PLC ) , calcium / calmodulin ( CaM ) , neuronal NOS ( nNOS ) and soluble guanylate cyclase , but not of protein kinase C and endothelial NOS ( eNOS ) , inhibited the carbachol action on detrusor contractility . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
In addition , the beta 3 adrenoceptor dependent increase in cGMP and activation of NOS were blocked by the inhibition of phospholipase C ( PLC ) , calcium / calmodulin ( CaM ) , endothelial NOS activity and cGMP accumulation . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Endothelial nitric oxide synthase ( eNOS ) is a calmodulin ( CaM ) dependent , membrane associated , myristoylated enzyme , which has an important role in regulation of vascular tone and platelet aggregation . ^^^ Membrane association can thus function to inhibit eNOS catalytic activity by interfering with the interaction of the enzyme with calmodulin . . ^^^ Binding of eNOS to PS vesicles prevents subsequent binding of the enzyme to CaM Sepharose . ^^^ Deletional mutation of the eNOS CaM binding domain , however , results in loss of binding capacity of the enzyme not only for CaM Sepharose but also for PS vesicles . ^^^ Furthermore , removal of the CaM binding domain converts eNOS from a membrane to a cytosolic protein when the enzyme is expressed in Sf 9 cells . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
The calmodulin ( CaM ) binding regions in bovine endothelial nitric oxide synthase ( eNOS ) and murine inducible nitric oxide synthase ( iNOS ) are identified in this study as eNOS residues 493 512 and iNOS residues 501 532 . ^^^ Peptides corresponding to eNOS 493 512 and NOS 501 532 produce a ( Ca2+ ) dependent , electrophoretic mobility shift of CaM on 4 M urea gels . ^^^ Substitution of eNOS and iNOS CaM binding domains in eNOS / iNOS chimeric proteins produces major alterations in the Ca2+ and CaM dependence of the intact enzymes expressed and purified from a baculovirus / Sf9 insect cell system . ^^^ Replacement of aligned NOS sequence with eNOS 493 512 creates a functional , chimeric iNOS that is both ( Ca2+ ) and CaM dependent . ^^^ Replacement of aligned eNOS sequence with NOS 501 532 creates a functional , chimeric eNOS that is CaM independent but that remains ( Ca2+ ) dependent . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
In this study , we have synthesized a 20 amino acid peptide corresponding to the putative calmodulin binding domain of human eNOS and studied the interaction of the peptide with calmodulin and with various membrane phospholipids . ^^^ These results suggest that the same domain of eNOS binds both calmodulin and membrane phospholipids . ^^^ Thus , our results raise the possibility that the calmodulin binding domain is directly involved in the membrane association of eNOS and that phosphorylation of the domain and Ca ( 2+ ) calmodulin may regulate the interaction . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Coexpression of CaM increases more than threefold the amount of expressed eNOS , stabilizes the recombinant protein , and significantly augments its specific activity ( to 140 170 nmol 10 min ( 1 ) 10 mg ( 1 ) at 37 degrees C ) . ^^^ These increases in activity are not achieved by the addition of CaM to eNOS expressed in the absence of CaM . ^^^ Gel filtration studies suggest that CaM coexpression produces a more elongated eNOS structure and alters the NADPH binding domain . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
In this study , wild type and mutant forms of eNOS have been expressed in a baculovirus system , and the quaternary structure of the purified enzymes has been analyzed by low temperature SDS PAGE . eNOS dimer formation requires incorporation of the heme prosthetic group but does not require myristoylation or CaM or BH 4 binding . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
The activity of the enzyme is regulated in vivo by calcium signaling involving the binding of calmodulin ( CAM ) , which triggers the activation of eNOS . ^^^ We have examined the possible role of calcium mediated CAM binding in promoting dimerization of eNOS through the oxygenase domain of the enzyme . ^^^ Binding of Ca2+ CAM caused an association of monomeric eNOS oxygenase domain as determined by changes in fluorescence , both intrinsic and extrinsic , and by gel filtration , chemical cross linking , and particle sizing . ^^^ A truncated form of the eNOS oxygenase domain lacking the Ca2+ CAM binding region did not undergo self association to form dimers . ^^^ These results show that the eNOS reductase domain is not required for Ca2+ CAM induced dimerization of eNOS and suggest that this dimerization may be a primary event in the activation of eNOS by Ca2+ . . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Like all known nitric oxide synthases , eNOS enzyme activity is dependent on Ca2+ calmodulin . eNOS is dynamically targeted to specialized cell surface signal transducing domains termed plasmalemmal caveolae and interacts with caveolin , an integral membrane protein that comprises a key structural component of caveolae . ^^^ We now report that in endothelial cells the interaction between eNOS and caveolin is importantly regulated by Ca2+ calmodulin . ^^^ Addition of calmodulin disrupts the heteromeric complex formed between eNOS and caveolin in a Ca2+ dependent fashion . ^^^ In addition , overexpression of caveolin markedly attenuates eNOS enzyme activity , but this inhibition is reversed by purified calmodulin . ^^^ We propose a model of reciprocal regulation of eNOS in endothelial cells wherein the inhibitory eNOS caveolin complex is disrupted by binding of Ca2+ calmodulin to eNOS , leading to enzyme activation . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
A synthetic peptide corresponding to caveolin 1 residues 82 101 also potently and reversibly inhibits eNOS activity by interfering with the interaction of the enzyme with Ca2+ / calmodulin ( CaM ) . ^^^ Regulation of eNOS in endothelial cells , therefore , may involve not only positive allosteric regulation by Ca2+ / CaM , but also negative allosteric regulation by caveolin 1 . . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Pretreatment with CaM peptide inhibits eNOS translocation . ^^^ In summary , the CaM peptide exhibits several anti inflammatory properties that include maintaining EC junctional stability and inhibiting eNOS translocation . . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Caveolin , the principal structural protein in caveolae , interacts with eNOS and leads to enzyme inhibition in a reversible process modulated by Ca2+ calmodulin ( Michel , J . ^^^ The inhibition of purified eNOS by the caveolin scaffolding domain peptide is competitive and completely reversed by Ca2+ calmodulin . ^^^ These studies establish that caveolin , via its scaffolding domain , directly forms an inhibitory complex with eNOS and suggest that caveolin inhibits eNOS by abrogating the enzyme ' s activation by calmodulin . . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
More recently , we have shown that association of eNOS with caveolin , the principal structural protein in caveolae , leads to enzyme inhibition , in a reversible process modulated by Ca2+ calmodulin ( CaM ) . ^^^ Finally , using transiently transfected COS 7 cells , we have observed that the myristoylation deficient cytosol restricted eNOS mutant ( myr ) as well as the cytosolic fraction of the palmitoylation deficient eNOS mutant ( palm ) may both interact with caveolin ; this association also leads to a marked inhibition of enzyme activity , which is completely reversed by addition of calmodulin . ^^^ We conclude that the regulatory eNOS caveolin association is independent of the state of eNOS acylation , indicating that agonist evoked Ca2+ / CaM dependent disruption of the caveolin eNOS complex , rather than agonist promoted depalmitoylation of eNOS , relieves caveolin ' s tonic inhibition of enzyme activity . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Endothelial nitric oxide synthase ( eNOS ) is targeted to caveoli through interaction with caveolin 1 ( cav 1 ) . cav 1 binding to a consensus site in the eNOS oxygenase domain is proposed to antagonize calmodulin ( CaM ) binding and thereby inhibit eNOS nitric oxide ( NO ) synthesis . ^^^ Cav 1P equivalently inhibited NO synthesis and NADPH oxidation by full length eNOS in a manner reversible by CaM but did not affect NADPH independent NO synthesis by full length eNOS or its oxygenase domain , indicating inhibition required the reductase domain . ^^^ Similar concentrations of cav 1P inhibited cytochrome c reduction by full length eNOS or the reductase domain ( amino acids 492 1205 ) in a CaM reversible manner , indicating cav 1P interaction with reductase or full length eNOS are equivalent . ^^^ The reductase interaction occurs independent of a cav 1 binding motif , is CaM reversible , and is of sufficient affinity to match cav 1P inhibition of NO synthesis by full length eNOS . ^^^ We propose that cav 1 binding to eNOS reductase compromises its ability to bind CaM and to donate electrons to the eNOS heme , thereby inhibiting NO synthesis . . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Ex vivo expression of nitric oxide synthase isoforms ( eNOS / iNOS ) and calmodulin in human penile cavernosal cells . ^^^ For indirect immunofluorescence and electron microscopy , cells were incubated overnight at 4C with specific primary ( eNOS ; calmodulin ) and secondary antibodies . ^^^ Localization studies showed positive signals for NADPH diaphorase , eNOS , and calmodulin . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Increasing vascular flow and pressure in situ rapidly activates caveolar eNOS with apparent eNOS dissociation from caveolin and association with calmodulin . ^^^ Hemodynamic forces resulting from increased flow appear to transmit through caveolae to release eNOS from its inhibitory association with caveolin , apparently to allow more complete activation by calmodulin and other possible effectors . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Calmodulin was necessary for the eNOS immunoreactivity : it was blocked by calmodulin antagonist W 7 ( 25 microM ) , but not by similar concentrations of the less potent calmodulin antagonist W 12 . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Shear induced upregulation of eNOS mRNA was unaffected by the calmodulin inhibitor W 7 and by the tyrosine kinase inhibitor herbimycin A , suggesting that neither calmodulin nor tyrosine kinases are required . ^^^ In conclusion , shear stress of BAEC increases eNOS transcriptional rate and upregulates eNOS mRNA levels by a process that requires calmodulin independent [ Ca2+ ] 1 signaling and a PTX sensitive G protein , is inhibited by PI 3 kinase , and is independent of microtubule integrity and tyrosine kinase activity . . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Shear stress and tyrosine phosphatase inhibitors have been shown to activate the endothelial NO synthase ( eNOS ) in a Ca2+ / calmodulin independent manner . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Here we show that AMPK co immunoprecipitates with cardiac endothelial NO synthase ( eNOS ) and phosphorylates Ser 1177 in the presence of Ca2+ calmodulin ( CaM ) to activate eNOS both in vitro and during ischaemia in rat hearts . ^^^ In the absence of Ca2+ calmodulin , AMPK also phosphorylates eNOS at Thr 495 in the CaM binding sequence , resulting in inhibition of eNOS activity but Thr 495 phosphorylation is unchanged during ischaemia . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
The activity of the endothelial isoform of NO synthase ( eNOS ) was recently shown to be modulated by its reciprocal interactions with the stimulatory Ca2+ calmodulin complex and the inhibitory protein caveolin . ^^^ Accordingly , higher calmodulin levels were required to disrupt the enhanced caveolin eNOS heterocomplex from HC serum treated cells . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Despite the correlation between reductase and overall enzymatic activity for the wild type and chimeric NOS proteins , the loop free eNOS still requires CaM to synthesize . ^^^ However , the reductive activity of the CaM free , loop deleted eNOS is enhanced significantly over that of CaM free wild type eNOS and approaches the same level as that of CaM bound wild type eNOS . ^^^ The eNOS insert not only inhibits activation of the enzyme by CaM but also contributes to the relatively low overall activity of this NOS isoform . . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
CaM controls eNOS dimerization rather then iNOS one . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Both nNOS and eNOS are activated by the reversible binding of calmodulin ( CaM ) in the presence of Ca ( 2+ ) , whereas inducible NOS binds CaM irreversibly . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Protein expression of endothelial NO synthase ( eNOS ) , caveolin , and calmodulin was examined by Western blotting and immunohistochemistry . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
More important , the APT 1 catalyzed depalmitoylation of palmitoyl eNOS is potentiated by Ca ( 2+ ) calmodulin ( CaM ) , a key allosteric activator of eNOS . ^^^ Taken together , these results support a role for APT 1 in the regulation of eNOS depalmitoylation and suggest that Ca ( 2+ ) CaM activation of eNOS renders the enzyme more susceptible to APT 1 catalyzed depalmitoylation . . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Consistent with its classification as a Ca2+ / calmodulin dependent enzyme the constitutive endothelial nitric oxide ( NO ) synthase ( eNOS ) can be activated by receptor dependent and independent agonists as a consequence of an increase in the intracellular concentration of free Ca2+ ( [ Ca2+ ] 1 ) and the association of the Ca2+ / calmodulin complex with eNOS . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Caveolins , the resident scaffolding proteins of caveolae , and calmodulin undergo reciprocal Ca2+ dependent association and dissociation with eNOS in the caveolar membrane that inhibits ( caveolins ) and activates ( calmodulin ) eNOS activity . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Enhanced electron flux and reduced calmodulin dissociation may explain `` calcium independent ' ' eNOS activation by phosphorylation . ^^^ These results suggest that a negative charge imposed at serine 1179 , either by phosphorylation or by replacement with aspartate , increases eNOS catalytic activity by increasing electron flux at the reductase domain and by reducing calmodulin dissociation from activated eNOS when calcium levels are low . . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
It has been postulated that a segment ( residues 594 645 ) inserted in the FMN subdomain of human endothelial nitric oxide synthase ( eNOS ) plays a crucial role in controlling Ca ( 2+ ) dependent CaM binding for eNOS activity . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Evidence that hsp 90 facilitates calmodulin stimulated displacement of eNOS from caveolin 1 . ^^^ Immunoprecipitation of Cav 1 from bovine lung microvascular endothelial cells shows that eNOS and hsp 90 are present in the Cav 1 complex . eNOS and hsp 90 from the lysate also interact with exogenous glutathione S transferase linked caveolin 1 ( GST Cav ) , and the addition of calcium activated calmodulin ( CaM ) to the GST Cav complex partially inhibited the association of eNOS and hsp 90 . ^^^ Purified eNOS associates with GST Cav specifically through the caveolin scaffolding domain ( residues 82 101 ) ; however , the addition of CaM slightly , but nonstatistically , reduces eNOS binding to GST Cav . ^^^ When hsp 90 is present in the binding reaction , the addition of increasing concentrations of CaM significantly displaces eNOS and hsp 90 from GST Cav . eNOS enzymatic activity is also less sensitive to inhibition by the caveolin scaffolding peptide ( residues 82 101 ) when eNOS is prebound to hsp 90 . ^^^ Collectively , our results show that the actions of CaM on eNOS dissociation from caveolin are facilitated in the presence of hsp90 . . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Truncated nNOS and eNOS plus calmodulin catalyzed NO formation at rates that were 45 and 33 % , respectively , those of their intact forms . ^^^ Without calmodulin , truncated nNOS and eNOS synthesized NO at rates 14 and 20 % , respectively , those with calmodulin . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Estradiol ( E ( 2 ) , 10 ( 8 ) mol / L ) caused an increase in eNOS activity in plasma membranes in the absence of added calcium , calmodulin , or eNOS cofactors , which was blocked by ICI 182 , 780 and ERalpha antibody . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Regulation of hepatic eNOS by caveolin and calmodulin after bile duct ligation in rats . ^^^ Additionally , caveolin 1 upregulation is associated with a significant reduction in NOS catalytic activity in BDL liver lysates , an event that is corrected with provision of excess calmodulin , a protein that competitively binds eNOS from caveolin . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
In the present study , we assessed whether the agonist induced ( Ca ( 2+ ) dependent , high output ) activation of eNOS is associated with changes in the phosphorylation of Thr ( 495 ) in the calmodulin ( CaM ) binding domain . eNOS Thr ( 495 ) was constitutively phosphorylated in porcine aortic endothelial cells and was rapidly dephosphorylated after bradykinin stimulation . ^^^ Little CaM was bound to eNOS immunoprecipitated from unstimulated cells , but the agonist induced dephosphorylation of Thr ( 495 ) enhanced the association of CaM . ^^^ Mutation of Thr ( 495 ) to alanine increased CaM binding to eNOS in the absence of cell stimulation , whereas the corresponding Asp ( 495 ) mutant bound almost no CaM . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
A specific inhibitor for CaM kinase 2 , KN 93 , and a calmodulin antagonist , W 7 , attenuated eNOS induction by H ( 2 ) O ( 2 ) . ^^^ Further studies have indicated that janus kinase 2 is important in mediating increased eNOS expression in response to H ( 2 ) O ( 2 ) and likely is downstream from CaM kinase 2 . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
A calmodulin inhibitor ( calmidizolium ) or removal of Ca2+ from the medium also blocked NO generation , indicating that endothelial NO synthase ( eNOS ) is the activated isoform . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Herein we discuss why other proteins , in addition to calmodulin , are necessary for eNOS regulation and summarize the biology of negative and positive regulators of eNOS function in vitro , in cells , and in blood vessels . . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Despite no observed difference in calmodulin affinity , CDelta 27 eNOS exhibited a 5 fold reduction in EC ( 50 ) for calcium and a 2 4 fold increase in maximal catalytic activities . ^^^ We conclude that the C terminus imposes a significant barrier to the activation of eNOS by calmodulin binding and that this barrier can be functionally disabled by Ser ( 1179 ) phosphorylation elicited enzyme activation . . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Hyperoxia did not alter eNOS association with Hsp 90 , nor did it modify nNOS or eNOS associations with calmodulin , the magnitude of eNOS tyrosine phosphorylation , or nNOS phosphorylation via calmodulin kinase . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Recent studies have demonstrated that estradiol ( E ( 2 ) ) activates eNOS in isolated endothelial plasma membranes in the absence of added calcium , calmodulin or eNOS cofactors . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
The two biochemical events appear to facilitate calmodulin access to its binding site . eNOS is upregulated at the transcriptional level . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
To test these hypotheses , EC were incubated with n LDL and then analyzed for * NO , O ( 2 ) ( * ) , phospho eNOS ( S 1179 ) , eNOS , Cav 1 , calmodulin ( CaM ) , and heat shock protein 90 ( hsp 90 ) . n LDL increased NOx by more than 4 fold while having little effect on A 23187 stimulated nitrite production . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Endothelial nitric oxide ( NO ) synthase ( eNOS ) is controlled by Ca ( 2+ ) / calmodulin and caveolin 1 in caveolae . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
However , eNOS was tightly coupled with caveolin 1 , and was dissociated from heat shock protein 90 or calmodulin in the hypoxic pulmonary artery in either the presence or absence of carbachol . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Herein , we show that a treatment of endothelial cells with a phospholipase C ( PLC ) inhibitor ( U 73122 ) , a calmodulin antagonist ( W 7 ) or with intracellular calcium chelators ( EGTA / AM , BAPTA / AM ) prevented VEGF mediated eNOS Ser ( 1177 ) phosphorylation and NO synthesis measured by cGMP production . 3 . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Calmodulin binds eNOS ( red ) at 1 : 1 stoichiometry and high affinity . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Although eNOS activity is coupled to changes in endothelial cell Ca ( 2+ ) levels , an increase in Ca ( 2+ ) alone is not sufficient to affect enzyme activity because the binding of calmodulin ( CaM ) and the flow of electrons from the reductase to the oxygenase domain of the enzyme is dependent on protein phosphorylation and dephosphorylation . ^^^ Two amino acids seem to be particularly important in regulating eNOS activity and these are a serine residue in the reductase domain ( Ser ( 1177 ) ) and a threonine residue ( Thr ( 495 ) ) located within the CaM binding domain . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Functional studies demonstrate that dyn 2 PRD selectively potentiates eNOS activity in a concentration dependent manner in an order of magnitude similar to that observed with dyn 2 full length and in a manner that requires calmodulin . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
This brief review summarizes the current state of knowledge with regard to regulation of eNOS through several distinct molecular mechanisms , each of which acts in concert with Ca2+ calmodulin ( CaM ) signaling in post translational activation of eNOS . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
In the presence of calmodulin ( CaM ) , HSP 90 increased eNOS activity dose dependently at both low and high Ca ( 2+ ) concentrations . ^^^ The EC ( 50 ) values of eNOS for both Ca ( 2+ ) and CaM were decreased in the presence of HSP 90 . ^^^ HSP 90 bound to eNOS in a dose dependent manner , and the amount of bound HSP 90 also increased with increasing Ca ( 2+ ) / CaM . ^^^ At 100 nm Ca ( 2+ ) , HSP 90 promoted dose dependent CaM binding to eNOS that was fully inhibitable by GA . ^^^ At high calcium , HSP 90 did not affect CaM binding to eNOS , but GA inhibited HSP 90 binding to eNOS . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Calmodulin ( CaM ) affinity , studied by radioligand binding using 125I labeled CaM , revealed virtually identical K ( D ) ( 3 . 2+ / 0 . 5 and 4 . 0+ / 0 . 3nM ) and B ( max ) ( 1 . 4+ / 0 . 2 and 1 . 2+ / 0 . 3 pmol / pmol subunit ) values for WT and E298D eNOS , respectively . ^^^ Calmodulin ( CaM ) affinity , studied by radioligand binding using 125I labeled CaM , revealed virtually identical K ( D ) ( 3 . 2+ / 0 . 5 and 4 . 0+ / 0 . 3nM ) and B ( max ) ( 1 . 4+ / 0 . 2 and 1 . 2+ / 0 . 3 pmol / pmol subunit ) values for WT and E298D eNOS , respectively . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Activation of eNOS by VEGF involves several pathways including Akt / PKB , Ca ( 2+ ) / calmodulin , and protein kinase C . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Estrogen receptors ( ERalpha and ERbeta ) , heat shock proteins ( hsp 70 and hsp 90 ) , endothelial nitric oxide synthases ( eNOS ) , caveolin 1 , 2 and 3 and calmodulin were analyzed in total platelet lysate by immunoblotting . ^^^ Expression of ERalpha and ERbeta , hsp 70 , hsp 90 , eNOS , calmodulin , and caveolin 1 were observed in both sexes . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
We propose that the calmodulin binding residues form a helix that is critical for the proper alignment of the adjacent reductase and oxygenase domains within the active eNOS dimer in achieving proper electron transfer between them . . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Synergistic activation of endothelial nitric oxide synthase ( eNOS ) by HSP 90 and Akt : calcium independent eNOS activation involves formation of an HSP 90 Akt CaM bound eNOS complex . ^^^ HSP 90 also facilitated CaM binding to eNOS irrespective of Akt presence . ^^^ Geldanamycin ( GA ) disrupted HSP 90 eNOS binding , reduced HSP 90 stimulated CaM binding , and blocked both recruitment of Akt to the eNOS complex and phosphorylation of eNOS at Ser 1179 . ^^^ Akt phosphorylated only CaM bound eNOS , in an HSP 90 independent manner . ^^^ GA prevented insulin induced association of HSP 90 , Akt and CaM with eNOS and inhibited eNOS activation in BAECs . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Inducible ( iNOS ) and constitutive ( eNOS , nNOS ) nitric oxide synthases differ in their Ca2+ calmodulin ( CaM ) dependence . iNOS binds CaM irreversibly but eNOS and nNOS , which bind CaM reversibly , have inserts in their reductase domains that regulate electron transfer . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Substitution of all nine methionine residues in CaM with leucines had minimal effects on the binding affinity or maximal enzyme activation for either the neuronal ( nNOS ) or endothelial ( eNOS ) isoform . ^^^ Site specific oxidation of Met ( 144 ) and Met ( 145 ) resulted in changes in the CaM concentration necessary for half maximal activation of nNOS and eNOS , suggesting that these side chains are involved in stabilizing the productive association between CaM and NOS . ^^^ However , the site specific oxidation of Met ( 144 ) and Met ( 145 ) had essentially no effect on the maximal extent of eNOS activation in the presence of saturating concentrations of CaM . ^^^ Thus , nNOS and eNOS exhibit different functional sensitivities to conditions of oxidative stress that are expected to oxidize CaM . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Here we report that bovine eNOS protein is phosphorylated at Thr 497 in the calmodulin binding domain by PKC both in vitro and in vivo , and that the phosphorylation negatively regulates eNOS activity . ^^^ Furthermore , the phosphorylated eNOS showed reduced affinity to calmodulin . ^^^ Therefore , PKC regulates eNOS activity by changing the binding of calmodulin , an eNOS activator , to the enzyme . . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
The enzymatic activities of eNOS or nNOS are induced by phosphorylation triggered by Ca ( 2+ ) entering cells and binding to calmodulin . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Here we have further elucidated the differential requirement of Ca2+ / CaM for enzyme activation between eNOS and iNOS by either deletion of residues 1165 1178 ( Delta 14 ) or combined deletions of residues 594 606 / 614 645 and 1165 1178 ( Delta45 / Delta 14 ) from eNOS to mimic iNOS . ^^^ The basal rates of double mutant Delta45 / Delta14 in NO production , NADPH oxidation , and cytochrome c reduction were 3 fold greater than those of CaM stimulated wild type eNOS . ^^^ The results suggest that the Ca2+ / CaM dependent catalytic activity of eNOS appears to be conferred mainly by these two structural elements , and the interdomain electron transfer from reductase to oxygenase domain does not require Ca2+ / CaM when eNOS lacks these two segments . . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
METHODS : Anti eNOS , anti caveolin 1 , and anti calmodulin antibodies were used for Western blotting . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Ca ( 2+ ) / calmodulin has no effect on the potentials of any of the couples in endothelial nitric oxide synthase ( eNOS ) or neuronal nitric oxide synthase ( nNOS ) . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
The endothelial NO synthase ( eNOS ) is regulated by diverse protein kinase pathways , yet eNOS activity ultimately depends on the ubiquitous calcium regulatory protein calmodulin ( CaM ) . ^^^ In these studies , we establish that CaM itself undergoes phosphorylation in endothelial cells and that CaM phosphorylation attenuates eNOS activation . ^^^ Phosphorylation of CaM by purified CK 2 in vitro reduces the 5 ( max ) of immunopurified eNOS by a factor of 2 but has no effect on the K ( A ) for CaM or calcium . ^^^ Additionally , we found that the phosphomimetic S101D CaM mutant is impaired in its ability to activate eNOS . ^^^ Taken together , these results suggest that phosphorylation of CaM inhibits eNOS catalysis and proceeds in a hierarchical manner , initially requiring phosphorylation of the CaM Ser 81 residue . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Levels of protein expression of endothelial NO synthase ( eNOS ) , caveolin 1 , and calmodulin were assessed in carotid arteries using Western analysis . ^^^ Expression of caveolin 1 was decreased , and calmodulin was increased , in vessels from daidzein or 17beta estradiol treated rats . eNOS expression was unaffected by the treatments . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Arginine , calmodulin or 2 , 5 ADP affinity purification protocols successfully concentrated eNOS and nNOS from full brain tissue but failed to show any signal in mitochondria . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
However , although the dephosphorylation of Thr ( 495 ) in histamine stimulated endothelial cells enhanced the binding of calmodulin to eNOS , calmodulin no longer bound to eNOS from ox LDL treated endothelial cells . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
The specificity of this effect was confirmed by the activation of oocytes by exogenous endothelial nitric oxide synthase ( eNOS ) microinjected in the oocyte with its activator calmodulin . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
While studies of human and bovine endothelial nitric oxide synthase ( eNOS ) demonstrate activation by Ca ( 2+ ) / calmodulin , recent progress demonstrates that eNOS phosphorylation can alter sensitivity to intracellular free calcium ( [ Ca ( 2+ ) ] ( 1 ) ) . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Effect of chronic ethanol administration on hepatic eNOS activity and its association with caveolin 1 and calmodulin in female rats . ^^^ We then tested the hypothesis that an imbalance between the binding of eNOS with inhibitory and stimulatory proteins may underlie the reduced activity of eNOS because eNOS catalytic activity is regulated partly through dynamic interactions with the inhibitory protein caveolin 1 and the stimulatory protein calmodulin . ^^^ The binding of caveolin 1 and calmodulin with eNOS was increased and decreased , respectively , in alcohol treated rats . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Historically eNOS has been thought to be a constitutively expressed enzyme regulated by calcium and calmodulin . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Protein level of eNOS , caveolin 1 and calmodulin was determined by Western blot . ^^^ Another eNOS stimulatory protein , calmodulin , was unchanged in these treatments . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
METHODS : Changes in caveolin 1 , calmodulin , and eNOS expression were determined by western blot and densitometric analysis . ^^^ RESULTS : Sinusoidal endothelial cells expressed caveolin 1 and calmodulin , and expression was altered in cultured and passaged cells . eNOS expression decreased significantly in 24 h cultured cells , with expression dropping below the level of detection in passaged cells . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Staurosporine , a general protein kinase inhibitor , also reduced phosphorylation and decreased calmodulin binding , an effect that may explain the reduction in activity . eNOS , therefore , is both an inhibitor of apoptosis and a target of apoptosis associated proteolysis . . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Inflammation was estimated by IL 8 mRNA expression and cellular adhesion molecules ( CAM ) . eNOS and iNOS message and eNOS protein served as an indirect measure for NO . ^^^ Sublethal superoxide dose evoked : ( 1 ) proinflammatory state manifested by increased IL 8 mRNA expression and CAM on the endothelial surface , ( 2 ) HUVEC apoptosis and activated endothelial NADPH oxidase , ( 3 ) increase in intracellular tissue factor , and ( 4 ) decrease in eNOS mRNA and protein and up regulation of iNOS mRNA . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
This was accompanied by significant glomerulosclerosis , tubulointerstitial damage , renal immune cell infiltration , marked down regulations of renal tissue eNOS and nNOS , mild reduction of caveolin 1 , and unchanged calmodulin , phospho AKt , and sGC . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
AIM : To determine whether biliary cirrhosis could induce pancreatic dysfunction such as modifications in endothelial nitric oxide synthase ( eNOS ) expression and whether the regulation of eNOS could be altered by the regulatory proteins caveolin and heat shock protein 90 ( Hsp 90 ) , as well as by the modifications of calmodulin binding to eNOS . ^^^ In contrast , cirrhosis decreased the calmodulin binding to eNOS with a concomitant decrease in eNOS activity . ^^^ CONCLUSION : In biliary cirrhosis , pancreatic injury is minor but the pancreatic nitric oxide ( NO ) production is significantly decreased by two mechanisms : a decreased expression of the enzyme and a decreased binding of calmodulin to eNOS . . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Tyrosine phosphorylation of eNOS and expression of calmodulin increased , but Hsp 90 decreased with all treatments and only raloxifene treatment increased caveolin 1 compared with OVX . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Endothelial nitric oxide synthase ( eNOS ) is regulated by multiple mechanisms including Ca ( 2+ ) / calmodulin binding , protein protein interactions , phosphorylation , and subcellular locations . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Interestingly , we also documented that the dissociation of the caveolin / eNOS heterocomplex induced by amlodipine was not mediated by the traditional calcium dependent calmodulin binding to eNOS and that recombinant caveolin expression could compete with the stimulatory effects of amlodipine on eNOS activity . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Largely assumed to be a Ca 2 ( + ) / calmodulin dependent enzyme , the endothelial constitutive nitric oxide ( NO ) synthase ( NOS 3 ) can be activated by agonists as a consequence of an increase in the intracellular concentration of free Ca2+ ( [ Ca2+ ] 1 ) . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Endothelium removal or NOS 3 inhibition with the calmodulin inhibitor , W 7 , increased NOS activity in the aortae of portal vein stenosed rats after LPS incubation . ^^^ Endothelium removal or calmodulin inhibition inhibits NOS 3 overactivity and leads to normalized NOS 2 activation after LPS in aortae from portal vein stenosed rats . . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Endothelial nitric oxide synthase ( NOS 3 ) is defined as being strictly dependent on Ca ( 2+ ) / calmodulin ( CaM ) for activity , although NO release from endothelial cells has been reported to also occur at intracellular free Ca ( 2+ ) levels that are substimulatory for the purified enzyme . ^^^ Phosphopeptide analysis by mass spectrometry identified Ser ( 1177 ) , as well as Ser ( 633 ) which is situated in a recently defined CaM autoinhibitory domain within the flavin binding region of human NOS 3 . ^^^ Importantly , both cAK and cGK phosphorylation of NOS 3 in vitro caused a highly reproducible partial ( 10 20 % ) NOS 3 activation which was independent of Ca ( 2+ ) / CaM , and as much as a 4 fold increase in 5 ( max ) in the presence of Ca ( 2+ ) / CaM . cAK stimulation in intact endothelial cells also increased both Ca ( 2+ / ) CaM independent and dependent activation of NOS 3 . ^^^ These data collectively provide new evidence for cAK and cGK stimulation of both Ca ( 2+ ) / CaM independent and dependent NOS 3 activity , and suggest possible cross talk between the NO and prostaglandin 1 ( 2 ) pathways and a positive feedback mechanism for NO / cGMP signaling . . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Thus , CaM dependent NOS 3 activation confers the selective Ca2+ sensitivity on 1 ( Ks ) . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
Catalytic activity of purified ecNOS in the absence of calmodulin was increased in a concentration dependent fashion by calreticulin . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
This deficiency is not due to a defect in the constitutive isoform of NO synthase in EC ( ecNOS ) or alterations in intracellular calcium , calmodulin , NADPH or arginine levels . ^^^
Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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Interacting proteins: P29474 and P62158	Pubmed	SVM Score :0.0
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